Proteomic analysis of peripheral leukocytes in Alzheimer's disease patients treated with divalproex sodium

Abstract

The molecular profiling of peripheral tissues, including circulating leukocytes, may hold promise in the discovery of biomarkers for diagnosing and treating neurodegenerative diseases, including Alzheimer's disease (AD). As a proof-of-concept, we performed a proteomics study on peripheral leukocytes from patients with AD both before and during treatment with divalproex sodium. Using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, we identified 10 differentially expressed proteins: two up-regulated proteins, 14-3-3 protein epsilon and peroxiredoxin 2; and eight down-regulated proteins, actin-interacting protein, mitogen activated protein kinase 1, beta actin, annexin A1, glyceraldehyde 3-phosphate dehydrogenase, transforming protein RhoA, acidic leucine-rich nuclear phosphoprotein 32 family member B, and a currently unidentified protein. A subset was validated on both the transcript and protein levels in normal human peripheral blood mononuclear cell cultures treated with valproic acid. These proteins comprise a number of functional classes that may be important to the biology of AD and to the therapeutic action of valproate. These data also suggest the potential of using peripheral leukocytes to monitor pharmaceutical action for neurodegenerative diseases.

Blood-Based Biomarkers of Alzheimer's Disease: Challenging but Feasible

“…They observed a significant association between plasma concentrations of CFH, A2M, APOE and complement C1 inhibitor and ADAS-Cog scores in AD patients treated with the highest doses of rosiglitazone (4 or 8 mg). In a similar study design, proteomic analysis of peripheral leucocytes was performed in AD patients before and after treatment with divalproex sodium [81]. Several proteins were differentially expressed in plasma after treatment and may be relevant to both disease processes in AD as well as to the mechanism(s) of action of divalproate sodium.…”

An update on clinical proteomics in Alzheimer’s research

“…One of the promises held by proteomics is its’ empowering capability to follow the influence of drug treatment on the proteome, making it possible to evaluate the efficiency of treatments. In a recent study, Mhyre et al. (2008) identified 10 differentially expressed proteins in human leukocytes in AD patients treated with divalproex sodium (Mhyre et al.…”

Pentoxifylline administration changes protein expression profile of coronary artery disease patients

“…The isolation of PBMCs requires separation of whole blood by centrifugation through a density gradient as it was described in previous studies (Dai et al, 2008;Dotzlaw et al, 2004;Mhyre et al, 2008). Whole blood was layered onto a sterile density gradient separation medium (CEDARLANE, Ontario, Canada) containing sodium diatrizoate at a predetermined density of 1.0770 g/mL at 22°C.…”

“…Furthermore, it was proven that the circulating monocytes are suitable to study the atherosclerosis process (Devaraj and Jialal, 2008). PBMCs have been used as surrogate reporter cells in studies on various pathologic conditions including Alzheimer (Mhyre et al, 2008), rheumatoid arthritis (Dotzlaw et al, 2004) and systemic lupus erythematosus (Dai et al, 2008).…”